Difficulties in collecting peripheral blood stem cells in chronic myeloid leukemia related to persistence of the leukemic cell clone.

Abstract

Eight chronic myeloid leukemia (CML) patients ineligible for allogeneic bone marrow transplantation (BMT) were intensively treated by a myeloablative chemotherapy identical to the treatment that we use in acute myeloid leukemia (AML). The objectives of such an intensive treatment were both to reduce the size of the leukemia stem cell mass as much as possible and subsequently to allow a better mobilization of the residual Ph-negative (Ph-) stem cells. Cytogenetic analyses were systematically performed on blood-derived stem cells collected at the hematopoietic recovery phase following post-chemotherapy aplasia. The length of aplasia did not correlate with the evolutive stage of the disease, but was negatively correlated with the total colony forming units-granulocyte macrophage (CFU-GM) amounts collected. The cytogenetic abnormality remained present in most cases in all metaphases counted in leukapheresis products. Three patients were transplanted with these leukapheresis products. One died due to sepsis before engraftment; the two others engrafted very slowly, while Ph-positive (Ph+) cells were found at post-transplant controls. These disappointing results suggest that the myeloablative chemotherapy used in this study has not resulted in satisfactory advantages for the proliferation of residual normal stem cells over the expansion of the Ph+ clone.